Evidence map›Paper›PMID 33706250›Full record

ArticleEBioMedicine2021

Altered iron and myelin in premanifest Huntington's Disease more than 20 years before clinical onset: Evidence from the cross-sectional HD Young Adult Study.

Eileanoir B Johnson, Christopher S Parker, Rachael I Scahill, Sarah Gregory, Marina Papoutsi, Paul Zeun, Katherine Osborne-Crowley, Jessica Lowe, Akshay Nair, Carlos Estevez-Fraga and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. In Vivo Mapping of Catecholaminergic Loss and Iron Deposition in Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

Eileanoir B JohnsonHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK. Electronic address: eileanoir.johnson@ucl.ac.uk.
Christopher S ParkerCentre for Medical Image Computing, Department of Computer Science, UCL, London, UK.
Rachael I ScahillHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Sarah GregoryHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Marina PapoutsiHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK; IXICO Plc, London, , UK.
Paul ZeunHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Katherine Osborne-CrowleyDivision of Equity, Diversity and Inclusion, University of New South Wales, Sydney, New South Wales, Australia.
Jessica LoweHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Akshay NairHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK; Max Planck University College London Centre for Computational Psychiatry and Ageing Research, UCL Queen Square Institute of Neurology, London, UK.
Carlos Estevez-FragaHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Kate FayerHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Geraint ReesUniversity College London Institute of Cognitive Neuroscience, University College London, London, UK.
Hui ZhangCentre for Medical Image Computing, Department of Computer Science, UCL, London, UK.
Sarah J TabriziHuntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK; Dementia Research Institute at University College London, London, UK.
HD-YAS Investigators
Huntington's Disease Association · GBUniversity College London · GBIxico (United Kingdom) · GBUNSW Sydney · AU

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundPathological processes in Huntington's disease (HD) begin many years prior to symptom onset. Recently we demonstrated that in a premanifest cohort approximately 24 years from predicted disease onset, despite intact function, there was evidence of subtle neurodegeneration. Here, we use novel imaging techniques to determine whether macro- and micro-structural changes can be detected across the whole-brain in the same cohort.

methods62 premanifest HD (PreHD) and 61 controls from the HD Young Adult Study (HD-YAS) were included. Grey and white matter volume, diffusion weighted imaging (DWI) measures of white matter microstructure, multiparametric maps (MPM) estimating myelin and iron content from magnetization transfer (MT), proton density (PD), longitudinal relaxation (R1) and effective transverse relaxation (R2*), and myelin g-ratio were examined. Group differences between PreHD and controls were assessed; associations between all imaging metrics and disease burden and CSF neurofilament light (NfL) were also performed. Volumetric and MPM results were corrected at a cluster-wise value of familywise error (FWE) 0.05. Diffusion and g-ratio results were corrected via threshold-free cluster enhancement at FWE 0.05.

findingsWe showed significantly increased R1 and R2*, suggestive of increased iron, in the putamen, globus pallidum and external capsule of PreHD participants. There was also a significant association between lower cortical R2*, suggestive of reduced myelin or iron, and higher CSF NfL in the frontal lobe and the parieto-occipital cortices. No other results were significant at corrected levels.

interpretationIncreased iron in subcortical structures and the surrounding white matter is a feature of very early PreHD. Furthermore, increases in CSF NfL were linked to microstructural changes in the posterior parietal-occipital cortex, a region previously shown to undergo some of the earliest cortical changes in HD. These findings suggest that disease related process are occurring in both subcortical and cortical regions more than 20 years from predicted disease onset.

Indexed as

AdultCase-Control StudiesCross-Sectional StudiesFemaleGray MatterHumansHuntington DiseaseIronLate Onset DisordersMagnetic Resonance ImagingMaleMyelin SheathWhite MatterYoung AdultIronHuntington's diseaseIronMicrostructureMRIMyelin

Identifiers

PMID33706250
PMCPMC7960938
OpenAlexW3134626930

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.